Carpal tunnel syndrome (CTS), the most common peripheral entrapment neuropathy, results from compression of the median nerve under the transverse carpal ligament at the wrist. It is an important occupational health problem because the frequency and severity of CTS cause more disability than virtually any other upper extremity disorder (Foley 2007). The ultimate goal of this research proposal is to reduce the incidence as well as the severity of CTS in working populations by elucidating the causes of both. Few prospective epidemiologic studies have the potential to assess the exposure-response relationships between biomechanical and psychosocial risk factors and either CTS or subsequent disability using rigorous case criteria and individual level exposure estimates. Even fewer are prospective with sufficient power to assess incidence and address sources of healthy worker survivor effect (HWSE) bias. HWSE has been shown to cause downward bias in occupational studies, and is a particular challenge in studies of musculoskeletal disorders such as CTS that are accompanied by discomfort (Arigghi 1994; Eisen and Robins 2001; Eisen 2005). There have been recent attempts to address the HWSE, using g-estimation in a mortality study of chronic heart and lung disease (Chevrier 2012), and inverse proportional treatment weights in a study of occupational asthma (Dumas 2013). However, there are no published longitudinal studies of CTS or subsequent work disability that address HWSE bias. In fact, other than a single cross-sectional study of garment workers (Punnett 1996), HWSE has not been taken into account when studying musculoskeletal disorders (Punnett 2004). If the workers exposed to repetitive and forceful movements consequently who develop CTS (including median nerve symptoms) are more likely to leave such work then those who remain exposed will be at lower risk. Such self-selection based on health status can reverse the causal direction and result in underestimation of the association between biomechanical risk factors, CTS, and subsequent work disability. The objective of this research is to estimate the association between biomechanical exposures, work psychosocial exposures, and CTS or CTS-related work disability while adjusting for downward bias from the HWSE. To address right truncation, inverse proportional censoring weights will be used in the analysis. To address left truncation, a sensitivity analysis will be performed by varying the date of hire criterion for entry into the pooed cohort. Adjustment for confounding from time-varying variables will utilize inverse proportional treatment weights. This approach to reducing HWSE bias has not been performed in a study of CTS or subsequent work disability because most studies of musculoskeletal disorders are not of adequate size or complexity. The findings of this research will help clarify the relationships between biomechanical, work psychosocial risk factors and the severity of CTS and CTS-related work disability that can facilitate the development of comprehensive prevention strategies.